Lack of medication for bipolar disorder is a calamity, say psychiatrists.
Since the beginning of this year, patients with bipolar disorder have had difficulty finding lithium carbonate in pharmacies and public services in São Paulo and various other parts of the country. The substance has a protective effect against the bouts of severe depression or mania (euphoria) that characterize the illness, as well as playing an essential role in preventing suicide.
The ABP (Brazilian Psychiatric Association) says that the situation is "calamitous" and that it is demanding answers from Anvisa (National Health Surveillance Agency), as well as support from health control and inspection bodies. The institution explains that lithium carbonate cannot be substituted for many patients, "under penalty of the possible worsening of psychiatric conditions and consequent increase in the number of suicide cases in Brazil, the demand for emergency services, in addition to the greater need for hospitalizations in a scenario of bed shortages".
Complaints from doctors and patients at Caps (Psychosocial Support Centers) and UBSs (Basic Health Units) have been frequent. On Thursday (5), São Paulo City Hall informed, through the Municipal Health Department, that Lithium Carbonate 300 mg is in short supply due to a lack of raw materials from manufacturers. "There is an open process for emergency purchase by the municipal administration, where companies interested in participating must submit their proposals by March 10," it added.
Abrata (the Brazilian Association of Families, Friends and Sufferers of Affective Disorders) has been receiving messages from patients from all over the country since mid-January, first about the lack of 450 mg ER lithium carbonate, and then 300 mg. The association hasn't done a survey, but it guarantees that there have been countless complaints, phone calls and comments in patient and family groups. "Around 90 people a week circulate in these face-to-face groups. And almost 100% of them use lithium carbonate," says vice-president Neila Campos.
Translator Lilia Loman, who has been using the drug for 28 years, has been looking for lithium in the pharmacies of the main chains in São Paulo, without success, for about a month. Despite contacting the customer service department of the manufacturer of Carbolitium, Eurofarma, several times and being told that 300 mg was available, she hadn't found anything until Thursday (5). On one occasion, she was referred to a pharmacy that only had one box, but soon discovered that it had been reserved for another buyer. Lilia also can't find any generics or similar products from other laboratories (Carlit and Litcar).
"The search has become an undesirable part of the routine, not just for me, but also for family and friends," she complains. She still has a few units of the medicine, "but with no prediction of when this shortage will actually last, the worry is enormous". The only time she went without lithium carbonate was during her pregnancy ten years ago: "It was an extremely difficult period, a relapse after many months of stability, with symptoms exacerbated by the lack of medication," she recalls. She experienced insomnia, depression, bouts of aggression and even suicidal ideation.
What the laboratories say
Tracing the source of the problem is not easy. The report contacted the three laboratories that sell lithium carbonate (Eurofarma, Hipolabor and Biolab), and two of them explained that the recent shortage was due to difficulties in acquiring raw materials from the manufacturer of the inputs, whose name was not revealed.
Eurofarma confirms the shortage of Carbolitium CR 450 mg, but says that production had resumed and that establishments across the country would begin to be supplied in March. The company emphasizes that there are other therapeutic alternatives on the market, such as Carbolitium 300 mg. "The medical profession is being informed and it is important that patients contact their trusted doctor to make the necessary substitutions and dosage adjustments." Like Lilia Loman, the report called some pharmacies in the capital, such as Onofre and Ultrafarma, and couldn't find the 300 mg product, either from Eurofarma or other laboratories.
Also contacted, Hipolabor, from Minas Gerais, said that "the forecast is that all the necessary medicines will be supplied by April. Later this month, the goal is to produce 20 million doses and, by the end of next month, another 30 million doses should be produced".
Biolab Genéricos, which claims to supply mainly the private network, says it is not having problems producing lithium carbonate. "On the contrary, the company tripled its supply of generic products in February 2020 compared to the same month last year: 22,000 boxes of 50 units (Feb 19) and 69,000 boxes of 50 units (Feb 20)," it said in the note, noting that the growth in supply occurred "even in the face of the explosive increase in raw material costs, which are dollarized."
The report received only a few clues about the supply problem: it was informed that the raw material for the drug lithium carbonate is national, comes from a single supplier, and that laboratories are prohibited from importing from other countries.
What does Anvisa say?
The Agency clarifies that there is no legal instrument preventing pharmaceutical laboratories from withdrawing medicines from the market. However, it explains that the regulations require companies to communicate the definitive or temporary discontinuation of the manufacture or import of medicines at least 180 days in advance. When the problem is due to something unforeseen, communication must take place within a maximum of 72 hours, and failure to comply with the rule results in penalties.
After consulting the database on lithium carbonate, Anvisa reported that there had been no notification, but pointed out that the medicines market fluctuates in terms of import procedures, storage, distribution chain, etc., which can affect points of sale. See the rest of the note sent by the agency:
"According to our databases, there was stock of the drug at the distributors on 01/2020. In response to the complaint, ANVISA notified the laboratory for clarification. In response, the laboratory said that, as it is a high-turnover product, there was no stock available at that time, and clarified that the operational actions to resume production were advanced so that the market would be replenished in March 2020. He also informed us that the drug Carbolitium CR® (lithium carbonate) 450 mg 30 extended-release tablets is experiencing a momentary shortage, due to complications in the production process. However, there are therapeutic alternatives on the market, such as Carbolitium® 300 mg. The medical profession is being informed so that treatments are not jeopardized. We are advising patients who contact Anvisa about this issue to contact their doctor about adjusting their medication until the situation is normalized. In view of the information that the company has not notified the discontinuation, administrative procedures have been taken to investigate the irregularity pointed out." For the Brazilian Psychiatric Association (ABP), which also denounces the lack not only of lithium, but also of the antidepressant imipramine hydrochloride, the drugs are not being produced by private laboratories and, unfortunately, are not yet available in Brazilian government laboratories. "The shortage or discontinuation of these drugs, which are off-patent and very cheap - if produced by the government, they would cost pennies to sell - would constitute a crisis in medical care, with the risk of immediate relapses of serious mental disorders," the institution said in a letter to the press.
Pharmacist and biochemist Dirceu Raposo de Mello, who chaired Anvisa from 2005 to 2010, also advocates that the government take advantage of the structure of public laboratories to correct cases of shortages caused by the lack of interest from pharmaceutical companies in drugs that, with the passage of time and increased competition, no longer generate a profit or even cause a loss. "When this situation arises, isn't it worth internalizing production?" he asks.
The former president of Anvisa cites other similar and dangerous scenarios, such as the recent shortage of benzathine penicillin, an old drug that is still used today to combat syphilis, including in newborns. Only four laboratories produce the substance worldwide, precisely because it is old and cheap. This puts Brazil, as well as other countries, in an extremely vulnerable situation at a time when authorities point to the uncontrolled increase in this sexually transmitted infection (STI).
"Penicillin for mental health"
Psychotherapist and medical education instructor Mark Ruffalo, from the University of Central Florida in the USA, is one of the professionals who compares lithium carbonate to the antibiotic that revolutionized the history of medicine. Although the therapeutic properties of water rich in lithium salts have been known since ancient Greece, it wasn't until the 1950s that the treatment for what was then known as "manic-depressive illness" was discovered. Studies with lithium, according to Ruffalo, preceded the first drugs used in psychiatry.
The instructor says that lithium prescription rates are low in the US compared to other countries, which he attributes largely to a lack of economic interest: "Lithium is very cheap, even for those who don't have health insurance. Since pharmaceutical companies have never been able to patent lithium, they have never invested in marketing [for the drug], so doctors today are much more likely to prescribe highly advertised second-generation antipsychotics and mood stabilizers."
Another issue pointed out by some studies about low prescribing in the US is that lithium carbonate requires knowledge on the part of doctors, prior examinations and continuous monitoring of the patient. It is necessary to test the levels of the substance in the patient's blood regularly, as any excess can have a toxic effect, especially on the thyroid or kidneys. Not to mention side effects such as nausea and tremors, which hinder adherence.
Despite all the risks, the effect seems miraculous for some patients. "I don't believe in God, but I do believe in lithium," sums up American writer Jaime Lowie, in one of the articles published about her struggle to control the manic episodes of the disorder she was diagnosed with at the age of 16. Jaime took the drug for more than two decades, but was forced to stop because prolonged use affected her kidney function. The impression you get from reading her texts is that even the threat hasn't changed her admiration for lithium. "In fact, I considered continuing, even though I knew I would end up needing a kidney transplant," she confirms.
In her book "Mental - Lithium, Love, and Losing my Mind", she not only talks about bipolar disorder, but also provides information about the element behind the medicine that brought her stability. To do her research, she consulted doctors, visited the Salar de Uyuni in Bolivia (which concentrates half of the world's lithium reserves), visited battery factories in America and spas that offer baths in waters with extra doses of the mineral. Jaime also regrets the current lack of interest in the drug. "There is research showing that lithium could be useful for dementia and Parkinson's, but it is very difficult to get funding to test whether this is true or not because there is no profit margin," he comments.
Today, the writer is doing well, but she warns that it took her about nine months of trying different mood stabilizers before she adapted to the current one. Psychiatric treatments often involve more than one drug, so there needs to be a fine-tuning that takes into account response, interactions and side effects. Finding the right combination, in partnership with the psychiatrist, always takes time and requires patience. An alchemy that shouldn't be threatened by economic issues.